With age comes a decline in the dynamic regulation of a balanced and functional mitochondrial proteome (proteostasis) that leads to an increase in oxidative stress and macromolecule damage, with a decline in ATP production. Compromised protein networks and reduced available energy leaves an organism susceptible to accelerated aging and the onset of age-related disease. Since mitochondrial respiratory complexes are composed of protein subunits from both mitochondria and nuclear genomes, their assembly relies on the coordination of mitochondrial and cytoplasmic translation machinery. Disruption of mitochondrial translation generates an imbalance in the ratio of mitochondrial (mtDNA) to nuclear DNA (nDNA) encoded proteins, which is called a mitonuclear protein imbalance. In response to the protein imbalance, a retrograde stress signal is sent from the mitochondria to the nucleus, invoking the mitochondrial unfolded protein response (UPRᵐᵗ) to resolve the mitoproteostatic stress. In a young healthy cell, the UPRᵐᵗ upregulates protein folding chaperones and proteases to resolve the consequences of a mitonuclear protein imbalance. In the early stages of aging, the UPRᵐᵗ appears to be upregulated in response to age-related mitochondrial proteostatic stress. In aged senescent cells however, the UPRᵐᵗ response is blunted. There is cross-species evidence that induction of the UPRᵐᵗ through moderate-intensity exercise or through genetic disruption of the mitochondrial translation machinery will act as a hormetic - resulting in health benefits in the long term. Caenorhabditis elegans longevity models demonstrate that a reduction in mitochondrial ribosomal protein (Mrp) gene expression or disturbed mitochondrial translation will function as a hormetic. The disruption of the mitochondrial ribosome leads to a mitonuclear protein imbalance, invokes the nematode UPRᵐᵗ, which then robustly extends C. elegans lifespan and health span. To determine whether the hormetic effects of mild mitochondrial ribosome disruption can be recapitulated in a mammalian model, this thesis tests a C57/BL6/NTaconic mouse model altered in the germline to have reduced Mrpl54 expression through heterozygous mutation. Mice were metabolically tested at ages 6-, 18-, and 24-months and followed through their natural lifespan to determine whether reduction in the expression of a critical Mrp (Mrpl54) impacts lifespan or metabolic health span. While Mrpl54 mRNA expression was ~50% of wildtype in all Mrpl54⁺ᐟ⁻ tissues tested, there were no differences observed in metabolic health with age or lifespan in either male or female mice. Cultured Mrpl54⁺ᐟ⁻ primary myoblasts had lower absolute levels of nDNA- and mtDNA-encoded respiratory complex subunits relative to wildtype; however, the ratio between nDNA- and mtDNA-encoded protein subunits remained like wildtype. Further testing of the model revealed that Mrpl54⁺ᐟ⁻ males had weaker grip strength by age 12-months, which was also found in the data from multiple heterozygous Mrp (Mrp⁺ᐟ⁻) mouse models available at the International Mouse Phenotyping Consortium. 12-month-old Mrpl54⁺ᐟ⁻ males displayed reduced tetanic force and better fatigue recovery in ex vivo skeletal muscles, and the transmission electron micrographs of skeletal muscle sarcomeres revealed an early aging phenotype. Unlike the C. elegans reduced Mrp longevity model, reduced expression of a critical Mrp did not result in lifespan or metabolic health span benefits in a mouse model. In contrast, the Mrpl54⁺ᐟ⁻ male model showed evidence of premature skeletal muscle aging. While the results of this research do not support the role of Mrpl54 reduced expression in mammalian lifespan or health span extension, they do point to a premature aging phenotype for certain muscle parameters that may be relevant to people living with heterozygous mitochondrial protein mutations. Typically, these individuals are regarded as carriers and free of phenotype associated with their mitochondrial protein mutation. The results in this thesis suggest that those with a heterozygous mitochondrial protein gene mutation may manifest a phenotype as they grow older and are less resilient to external or internal challenges.